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Purpose Our research aimed to investigate the expression level of circ_0002232, which is transcribed from PTEN, and find out the association of circ_0002232/miR-92a-3p/PTEN network in acute myeloid leukemia (AML). Methods Circ_0002232 expression in 115 AML patients and 48 controls was detected by using real-time quantitative PCR. The diagnostic value of circ_0002232 expression was evaluated by receiver operating characteristic curve. Kaplan-Meier curves were used to analyse the impact of circ_0002232 for overall survival. Associated network of circ_0002232 was predicted by using interaction prediction websites. Results Compared with controls, circ_0002232 was notably low-expressed in AML (P

Background: Altered expression of the BCL-2 family member MCL-1 has been linked to the progression and outcome of various malignancies. Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application. Purpose: Herein, we reported MCL-1 expression pattern in Chinese de novo acute myeloid leukemia (AML) and its impact on prognosis and may provide theoretical basis for AML patients using MCL-1 inhibitor in clinics. Real-time quantitative PCR was carried out to detect the transcript of MCL-1 in AML patients. Results: MCL-1 expression was significantly up-regulated in AML compared with controls (P=0.042). We divided the patients into two groups (higher and lower expression of MCL-1) based on the median level. Among both non-acute promyelocytic leukemia (APL) and cytogenetically normal AML (CN-AML), patients with higher expression of MCL-1 correlated with lower complete remission (CR) rate (P=0.031 and 0.004, respectively) and shorter overall survival (OS) time (P=0.008 and 0.004, respectively) compared with those with lower expression of MCL-1. Meanwhile, Cox regression analyses revealed that overexpression of MCL-1 acted as an independent risk factor for OS in non-APL patients and CN-AML patients (P=0.011 and 0.045, respectively). In follow-up patients, MCL-1 expression level decreased after CR compared with newly diagnosis time (P=0.020) and increased after relapse (P=0.004). Conclusion: Our findings suggest that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring.

DOK-1 and DOK-2 (DOK1/2) are closely related members of downstream of tyrosine kinase (DOK) family genes, which are found to be frequently rearranged in several hematopoietic cancers. However, the clinical implications of DOK1/2 in acute myeloid leukemia (AML) remain largely unknown. To investigate the clinical significance, real-time quantitative PCR (RQ-PCR) was carried out to detect DOK1/2 expressions in 125 de novo AML patients and 28 healthy controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were applied to detect DOK1/2 methylation level and density. DOK1/2 expressions were significantly down-regulated in AML patients. The promoters of DOK1/2 were highly hypermethylated and negatively correlated with DOK1/2 expressions in AML patients. In addition, we also confirmed that DOK1/2 expressions could be restored by DOK1/2 demethylation using 5-aza-2'-deoxycytidine in leukemia cell line THP-1. Survival analyses showed that low-expressed DOK1/2 were associated with markedly shorter overall survival and leukemia free survival in both whole-cohort AML and non-M3 AML patients. Multivariate analyses further revealed that DOK1/2 were act as independent prognostic factors in AML patients. These findings indicate that decreased DOK1/2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML.

Accumulating studies have shown that miR-216b acted as a tumor suppressor and was down-regulated in solid tumors. However, little studies revealed the role or clinical implication of miR-216b in blood cancers. Herein, we reported miR-216b expression and its clinical significance in patients with acute myeloid leukemia (AML). In the current study, we analyzed bone marrow (BM) miR-216b expression in 115 de novo AML patients examined by real-time quantitative PCR. Notably, BM miR-216b expression was significantly up-regulated in AML patients, and could serve as a potential biomarker distinguishing AML from controls. No significant correlations of BM miR-216 expression were found with sex, age, white blood cells, hemoglobin, platelets, BM blasts, French-American-British classifications, and karyotypes. Significantly, patients with high miR-216b expression tended to have a lower frequency of FLT3-ITD mutation and higher incidence of U2AF1 and IDH1/2 mutations. Moreover, complete remission (CR) rate and overall survival were negatively affected by BM miR-216b overexpression among cytogenetically normal AML (CN-AML). Cox regression analyses showed that high BM miR-216b expression may act as an independent risk factor in CN-AML patients. Among the follow-up patients, BM miR-216b level in CR phase was markedly lower than in diagnosis time, and was returned in relapse phase. Collectively, our findings indicated that miR-216b overexpression was a frequent event in de novo AML, and independently conferred a poor prognosis in CN-AML. Moreover, miR-216b expression was a valuable biomarker correlated with disease recurrence in AML.

// Jing-Dong Zhou 1, 3, * , Ji-Chun Ma 2, 3, * , Ting-Juan Zhang 1, 3, * , Xi-Xi Li 1, 3 , Wei Zhang 1, 3 , De-Hong Wu 4 , Xiang-Mei Wen 2, 3 , Zi-Jun Xu 2, 3 , Jiang Lin 2, 3 and Jun Qian 1, 3 1 Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China 2 Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China 3 The Key Lab of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People’s Republic of China 4 Department of Hematology, The Third People’s Hospital of KunShan City, Suzhou, Jiangsu, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jun Qian, email: qianjun0007@hotmail.com Jiang Lin, email: linjiangmail@sina.com Keywords: ID2, expression, prognosis, TCGA, AML Received: June 22, 2017 Accepted: August 09, 2017 Published: September 01, 2017 ABSTRACT Dysregulation of ID proteins is a frequent event in various human cancers and has a direct role in cancer initiation, maintenance, progression and drug resistance. Our previous study has revealed ID1 expression and its prognostic value in acute myeloid leukemia (AML). Herein, we further reported ID2 expression and its clinical significance in AML. Real-time quantitative PCR was performed to detect ID2 transcript level in bone marrow mononuclear cells of 145 de novo AML patients. ID2 expression was significantly up-regulated in AML patients compared with controls. ID2 overexpression occurred with the highest frequency in poor karyotype (10/17, 59%), lower in intermediate karyotype (35/83, 42%), and the lowest in favorable karyotype (7/40, 18%). Moreover, high ID2 expression correlated with lower complete remission (CR) rate, shorter overall survival, and acted as an independent prognostic biomarker in whole-cohort AML and non-M3-AML patients. Importantly, the prognostic value of ID2 expression in AML was validated by The Cancer Genome Atlas (TCGA) data. In the follow-up of patients, ID2 expression at CR phase was decreased than at the time of diagnosis, and was increased again at the time of relapse. These findings demonstrated that bone marrow ID2 overexpression was a frequent event in AML patients, and predicts poor chemotherapy response and prognosis.

In addition to the appealing semiconducting properties displayed by layered SnII or PbII halidometallates, intriguing phase-transition-induced properties, such as dielectric and ferroelectric properties, have recently been found by us in (benzylammonium)2PbCl4 and (cyclohexylammonium)2PbBr4–4xI4x (x = 0–1). The simple molecular structures of the layered compounds allow further chemical design for the modification of the physical properties. Thus, we extended the study to layered compounds templated by structurally similar organic cations to achieve future functions. Here, we report the design of a layered perovskite templated by cyclohexylmethylammonium cations, namely, bis[(cyclohexylmethyl)ammonium] tetrabromidolead(II). We found that this compound exhibits not only photoluminescence with a remarkably high efficiency (quantum yield = 21 %) but also interesting phase-transition-related physical properties, such as striking dielectric responses. These results reveal the great application potential of organic–inorganic hybrid compounds in the field of phase-transition multifunctional materials. More interesting phase-transition crystals are expected to be tailored in the future by taking advantage of the richness of layered perovskites.

To investigate the efficacy and safety of decitabine combined with half-course pre-excitation for the treatment of elderly patients with acute myeloid leukemia (AML).44 cases of newly diagnosed elderly AML admitted in our hospital from January 2016 to December 2017 were selected for the retrospective analysis. The patients were randomly divided into 2 groups: pre-excitation therapy group as control and combined therapy group. The 22 patients in pre-excitation therapy group reccived the routine complete course pre-excitation treatment, 22 patients in combined therapy group received the desitabine combined the half course pre-excitation treatment. The therapentic efficacy and adverse reactions during treatment were compared between 2 groups. All patients were followed-up and the survival rate at 6,12 and 24 months was compared between 2 groups.The remission rate(RR) in the combined therapy group was 72.73%, and that in the control group was 50.00%, with significant statistically difference (P0.05). The median survival time in combined therapy group (17.82±4.19 months) and control group (12.43±3.71 months) was statistically significant (P0.05). The rate of adverse reactions of digestive tract in combined therapy group was 40.91%, which was higher than that in control group (18.18%), and the difference of two groups was statistically significant (P0.05). The incidence of adverse reactions in blood system and bone marrow suppression in combined therapy group was 9.09% and 68.18%, which were lower than those in control group (27.27% and 95.45%), with statistically significant differences (P0.05). There was no statistically significant difference in the incidence of liver dysfunction, cardiac insufficiency and hair loss between the two groups (P0.05). The incidence of pulmonary infection, intestinal infection and other complications in combined therapy group was 13.64%, which was lower than that in control group 31.82%, and the difference of two groups was statistically significant (P0.05). No serious complications such as arteriovenous thrombosis occurred in either group, and no patients died during chemotherapy.Combination of disitamine and half-course prestimulation treatmentis is a safe and effective and elderly patients with AML shown a good tolerance.地西他滨联合半程预激方案治疗老年急性髓系白血病患者的疗效与安全性观察.观察地西他滨联合半程预激方案治疗老年急性髓系白血病（AML）患者的疗效与安全性.选择本院2016年1月-2017年12月44例初诊的老年AML患者进行回顾性分析。根据治疗方案将患者分为2组：预激治疗组作为对照（22例）和联合治疗组（22例），前者采用常规全程预激治疗，后者采用地西他滨联合半程预激方案治疗。比较疗效和治疗期间副反应。所有患者均进行随访，比较2组6个月、12个月、24个月的生存率.联合治疗组RR为72.73%，对照组RR为50.00%，差异有统计学意义（P＜0.05）。联合治疗组中位生存时间为17.82±4.19个月，明显优于对照组中位生存时间（12.43±3.71个月）（P＜0.05）。联合治疗组消化道不良反应率为40.91%，明显高于对照组（18.18%）（P＜0.05）。联合治疗组血液系统不良反应率、骨髓抑制率分别为9.09%、68.18%，均明显低于对照组（27.27%和95.45%）（P＜0.05）。2组肝功能异常、心功能不全及脱发发生率差异无统计学意义(P＞0.05)。联合治疗组肺部感染、肠道感染等并发症发生率为13.64%，明显低于对照组（31.82%）（P＜0.05）。2组均无动静脉血栓等严重并发症发生，化疗期间无患者死亡.地西他滨联合半程预激方案治疗老年AML患者耐受性好，是适合老年AML患者安全有效的方法.

To investigate the predictive effect of platelet activation index expression before and after adenosine bisphosphate activation on bleeding risk in patients with primary immune thrombocytopenia (ITP).Eighty-nine patients with ITP admitted in our hospital from January 2017 to October 2018 were selected and inrolled in ITP group, the bleeding scoreing and grading were performed by using the ITP-BAT for ITP patients, then 89 ITP patients were divided into 4 subgroups: nothing bleeding symptom group, mild bleeding symprom group, mode rate bleeding symptom group and severe bleeding symptom group according to bleeding scores and grades obtained from ITP-BAT detection. At the same time, 22 persons underwent the health physical examination were selected and enrolled in control group. The adenosine diphosphate (ADP) was used as activator for all patients and controls. The flow cytonetry was used to analyze the expression of platelet membranc glyco protein (GPⅠb, GPⅡb /Ⅲ a) and P-selectin before and after ADP activation, the multiple linear person's correlation analysis was used to analyze the correlation of bleeding degree of ITP patients before and after ADP acbivation with the expression levels of GPⅠb, GPⅡb/Ⅲa and P-selectin.After the ADP activation, the expression level of GPⅠb significantly decreased, while the expression levels of GPⅠb, GPⅡb/Ⅲ a and P-selectin significantly increased in control group, nothing bleeding symptom group and mild bleeding symptom group; but the expression level of GPⅠb significantly increased, while the expression level of GPⅡb/Ⅲ a significantly decreased in moderate and severe bleeding symptom group, the both differences were statistically significant (P＜0.05). however, the expression level of P-selectin in moderate and severe bleeding symptom groups before and after ADP activation was not statistivally significant (P＞0.05). Before ADP activation, the expression level of GPⅠb in ITP subgroups was lower than that in control group, the expression level of GPⅡb/Ⅲ a in ITP subgroups was higher than that in control group, the expression level of P-selectin in moderate and severe bleeding symptom groups was higher than that in control group (P＜0.05). After ADP activation, the expression levels of GPⅠb and P-selectin in ITP subgroups both were lower than those in control group, the expression level of GPⅡb/Ⅲa in ITP subgroups was higher than that in control group (P＜0.05). The comparison among ITP subgroups showed that before ADP activation, the expression level of GPⅠb in moderate and severe bleeding symptom groups was lower than that in nothing bleeding symotom and mild bleeding symptom groups, while the expression levels of GPⅡb/Ⅲa and P-selectin were higher than those in nothing bleeding symptom and mild bleeding symptom groups (P＜0.05), however, after ADP activation, the expression level of GPⅠb in moderate and severe bleeding symptom groups was higher than that in nothing bleeding symptom and mild bleeding symptom groups, while the expression levels of GPⅡb/Ⅲ a and P-selection in moderate and severe bleeding symptom groups were lower than those in nothing and mild bleeding symptom groups (P＜0.05). The correlation analysis showed that before ADP activation, the expression levels of GPⅠb and GPⅡb/Ⅲa positivdy correlated with the bleeding risk (r=0.483, 0.504), and the P-selectin not correlated with the bleeding risk (r=0.000); however, after ADP activation, the expression level of GPⅠb and GPⅡb/Ⅲ a negatively correlated with the bleeding risk (r=-0.627, -0.406, -0.108).The expression level of platelet activation indicators before and after ADP activation is of certain value for prevention of bleeding risk in ITP patients and can be used as a reference indicator for the treatment and efficacy evaluation.ITP患者二磷酸腺苷激活前后血小板活化指标表达对患者出血风险的预测作用研究.研究原发免疫性血小板减少症（ITP）患者二磷酸腺苷激活前后血小板活化指标表达对患者出血风险的预测作用.选择我院2017年1月- 2018年10月住院治疗的ITP患者89例为ITP组，采用ITP 特异性出血评价工具（ITP-BAT）进行出血评分及出血程度分级。根据出血程度分为4个亚组：无出血症状组（19例），轻度出血组（32例），中度出血组（27例），大量及严重出血组（11例）。选择同期健康体检者22例为对照组，所有受检者均以二磷酸腺苷（ADP）为激活剂，应用流式细胞术检测激活前后血小板膜糖蛋白（GP）Ⅰb、Ⅱb/Ⅲa 和P选择素表达，分析GPⅠb、GPⅡb/Ⅲa、P选择素表达。采用Pearson多重线性相关性分析ADP激活前后ITP患者出血程度与GPⅠb、GPⅡb/Ⅲa、P 选择素表达水平的相关性.对照组、无症状组、轻度症状组ADP激活后GPⅠb表达水平显著下降，GPⅡb/Ⅲa、P 选择素表达水平显著升高；中度症状组、重度症状组ADP激活后GPⅠb表达水平显著升高，GPⅡb/Ⅲa表达水平显著降低，差异均有统计学意义（P＜0.05）。中度症状组、重度症状组ADP激活前后P选择素表达水平差异无统计学意义（P＞0.05）。ADP激活前ITP各亚组GPⅠb表达水平低于对照组，GPⅡb/Ⅲa表达水平高于对照组，中度症状组、重度症状组P 选择素表达水平高于对照组，差异均有统计学意义（P＜0.05）。ADP激活后ITP各亚组GPⅠb 、P选择素表达水平均低于对照组，GPⅡb/Ⅲa表达水平高于对照组，差异均有统计学意义（P＜0.05）。ITP各亚组比较显示，ADP激活前中度症状组、重度症状组GPⅠb表达水平低于无症状组、轻度症状组；GPⅡb/Ⅲa、P 选择素表达水平高于无症状组、轻度症状组，差异均有统计学意义（P＜0.05）。ADP激活后中度症状组、重度症状组GPⅠb表达水平高于无症状组、轻度症状组； GPⅡb/Ⅲa、P 选择素表达水平低于无症状组、轻度症状组，差异均有统计学意义（P＜0.05）。相关分析显示，ADP激活前GPⅠb、GPⅡb/Ⅲa表达水平与出血风险呈正相关（r=0.483，0.504）；P-选择素与出血风险不相关（r=0.000）；ADP激活后GPⅠb、GPⅡb/Ⅲa和P-选择素表达水平与出血风险呈负相关（r=-0.627， -0.406，-0.108）.ADP激活前后血小板活化指标表达水平对预防ITP患者出血风险有一定的价值，可以作为治疗和疗效观察的参考指标.

Background MicroRNA-29c (miR-29c) is abnormally expressed in several cancers and serves as an important predictor of tumor prognosis. Herein, we investigate the effects of abnormal miR-29c expression and analyze its clinical significance in acute myeloid leukemia (AML) patients. In addition, decitabine (DAC) has made great progress in the treatment of AML in recent years, but DAC resistance is still common phenomenon and the mechanism of resistance is still unclear. We further analyze the influences of miR-29c to leukemic cells treated with DAC. Methods Real-time quantitative PCR (RQ-PCR) was carried out to detect miR-29c transcript level in 102 de novo AML patients and 25 normal controls. miR-29c/shRNA-29c were respectively transfected into K562 cells and HEL cells. Cell viability after transfection was detected by cell counting Kit-8 assays. Flow cytometry was used to detect apoptosis. Results MiR-29c was significantly down-regulated in AML (P

Dysregulation of miR-378 has been found in diverse types of tumors as well as in leukemia. The role of miR-378 in chronic myeloid leukemia (CML) remains unclear. The aim of the study was to reveal the potential effects of miR-378 in the pathological process and progress in CML. Our results showed general level of miR-378 was significant higher in CML patients compared to controls. Overexpression of miR-378 dramatically promoted cell proliferation and drug-resistance. Additionally, apoptosis was inhibited in cells transfected with miR-378. More and bigger stem cell sphere formation was observed in miR-378 transfected cells. Furthermore, enhanced expression of miR-378 was associated with upregulation of stem-cell makers OCT4 and c-Myc. Further study validated that miR-378 inhibited the expression of FUS1. Our research demonstrated the oncogenic nature of miR-378 in CML, and might contribute to the progress of CML.

Compounds showing multi-switchable properties represent a type of new multi-stimuli responsive material that would find some promising applications. In this study, an organic–inorganic hybrid crystal (TA)2{(H3O)[Co(CN)6]} (1, TA = thiazolium) with a two-dimensional network constructed by the [Co(CN)6]3− anions and the hydronium cations via hydrogen-bonds was synthesized. 1 undergoes a structural phase transition between two polar phases at about 230 K due to the order–disorder transition of the TA cation. Detailed characterization, including variable-temperature structural analyses, differential scanning calorimetry (DSC), second-harmonic generation (SHG), dielectric and pyroelectric measurements, indicate that the local structural changes trigger multi-switchable properties of the dielectric constant, SHG and polarization. The discovery of multi-switchable responses based on polar compounds might provide a good strategy to search for new promising materials for smart switches.

A bistable optical–electrical duple switch belongs to a class of highly satisfying intelligent materials that can transform optical and electrical responses simultaneously in one device. A perovskite-type high-temperature phase transition compound with one-dimensional chain-like crystal structure, ([(CH3)3PCH2OCH3][PbBr3], 1), displays remarkable bistable photoluminescent-dielectric duple switching behaviors. The noteworthy order–disorder transition of the phosphonium cation and the motions of anions contribute to the phase transition, leading to the space group P21/c at a low temperature phase to C2/c at a high temperature phase. 1 exhibits a prominent step-like dielectric anomaly at 401.0 K and demonstrates novel optical properties with a band gap of 3.54 eV. The photoluminescence intensity suddenly declines from 398 K to 408 K, which may be attributed to the occurrence of phase transition. The electron cloud distributions of the frontier orbital in compound 1 have been calculated using a DFT program.

A new organic–inorganic hybrid compound [(CH3)3PCH2OH][Cd(SCN)3] (1) has been synthesized, which exhibits a reversible phase transition at 248.5 K confirmed by differential scanning calorimetry. The phase transition in 1 is from a centrosymmetric space group Pmcn to a non-centrosymmetric space group P21, so that 1 exhibits a switchable second harmonic generation (SHG) effect between SHG-on and SHG-off states. This phase transition also displays switchable dielectric behaviors between high and low dielectric states accompanied by the remarkable dielectric relaxation described by the Cole–Cole equation. Variable-temperature single-crystal X-ray diffraction analyses reveal that the origin of the phase transition can be attributed to the motion or reorientation of the [(CH3)3PCH2OH]+ cations and the movement of (SCN)− ions in solid-state crystals. These superior physical properties suggest that 1 could be a potential switchable dielectric and NLO relaxor-type material, which provides a new approach to design novel multiple switch materials.

The current study was aimed to investigate integrin beta-like 1 (ITGBL1) methylation pattern and its clinical relevance in patients with acute myeloid leukemia (AML). Real-time methylation-specific polymerase chain reaction (PCR; RQ-MSP) and bisulfite sequencing PCR (BSP) were performed to detect the methylation of ITGBL1 promoter. Real-time quantitative PCR (RT-qPCR) was performed to analyze ITGBL1 transcript level. The results showed that ITGBL1 methylation level in 131 patients with AML was significantly higher than 29 controls (p < 0.001). The ITGBL1-hypermethylated group tended to have a higher bone marrow (BM) blasts ( p = 0.076). Meanwhile, ITGBL1-hypermethylated patients tended to have a lower complete remission (CR) rate ( p = 0.102). ITGBL1-hypermethylated patients had significantly shorter overall survival (OS) and leukemia-free survival (LFS) than ITGBL1 hypomethylated patients in whole AML cohort ( p = 0.009 and 0.043, respectively) and patients with nonacute promyelocytic leukemia (APL ; p = 0.023 and 0.039, respectively). Multivariate analysis confirmed that the ITGBL1 methylation served as an independent prognostic factor in both patients with whole-cohort AML ( p = 0.030) and patients with non-APL ( p = 0.020). Furthermore, the ITGBL1 methylation level was significantly decreased in follow-up AML patients who achieved complete remission after induction therapy ( P = 0.001). ITGBL1 methylation negatively correlated with ITGBL1 expression in patients with AML ( R = -0.328, p = 0.008). Moreover, demethylation of ITGBL1 could increase the ITGBL1 expression in the K562 leukemic cell line ( p < 0.05). In conclusion, the ITGBL1 hypermethylation is a potential biomarker for predicting prognosis and monitoring disease status in patients with AML.

Background Leukemia stem cell (LSC)-enriched genes have been shown to be highly prognostic in acute myeloid leukemia (AML). However, the prognostic value of tumor suppressor genes (TSGs) that are repressed early in LSC remains largely unknown. Methods We compared the public available expression/methylation profiling data of LSCs with that of hematopoietic stem cells (HSCs), in order to identify potential tumor suppressor genes in LSC. The prognostic relevance of PCDH17 was analyzed on a cohort of 173 AML patients from The Cancer Genome Atlas (TCGA), and further validated in three independent cohorts (n = 339). Results We identified protocadherin17 (PCDH17) and demonstrated that it was significantly down-regulated and hypermethylated in LSCs compared with HSCs. Our analyses of primary AML patient samples also confirmed these deregulations. Clinically, low PCDH17 expression was associated with female sex (P = 0.01), higher WBC (P

Background Somatic mutations in SETBP1 gene have recently been detected in hematologic malignancies. The present study aimed to explore the frequency and clinical correlations of SETBP1 mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods In this study, we used high-resolution melting analysis (HRMA) to detect the SETBP1 mutations in a cohort of 363 patients with AML or MDS. Results A total of 1.2% (3/249) of AML and 1.8% (2/114) of MDS patients were found with heterozygous SETBP1 mutations. In AML, patients with SETBP1 mutations showed higher hemoglobin (P = 0.004) and were more frequently recurrent in AML-M4 subtype (P = 0.034). All five SETBP1 mutated patients had normal karyotypes. The patients with SETBP1 mutations had significantly higher incidences of concurrent SRSF2 mutations (P = 0.002). HRMA could detect SETBP1 mutations with 5% sensitivity, obviously higher than 25% of Sanger sequencing. Conclusions We established a rapid, inexpensive, high-throughput and sensitive method to screen SETBP1 mutations. SETBP1 mutations were a rare molecular event in AML and MDS patients.

Previous studies have been indicated that integrin α2 (ITGA2) may be important in cell migration, invasion, survival, and angiogenesis. However, the correlation between ITGA2 expression and acute myeloid leukemia (AML) is still unclear. Real-time quantitative polymerase chain reaction was carried out to analyze ITGA2 messenger RNA level. Methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing PCR were performed to detect the methylation of ITGA2 promoter. ITGA2 expression was significantly upregulated in 134 de novo AML patients compared with 33 controls (p = 0.007). ITGA2high group had markedly lower complete remission (CR) rate than ITGA2low group (p = 0.011). Furthermore, the overall survival in ITGA2high patients was significantly shorter than ITGA2low patients throughout AML cohort, non-acute promyelocytic leukemia (APL) and cytogenetic normal-AML (p = 0.001, 0.002, and 0.044, respectively). Multivariate analysis confirmed that ITGA2 overexpression served as an independent prognostic factor in both whole-cohort AML patients (p = 0.018) and non-APL AML patients (p = 0.021). Besides, ITGA2 expression level was significantly decreased in AML patients after CR (p = 0.011), and was returned at the time of relapse phase (p = 0.021). Moreover, unmethylated ITGA2 promoter was identified in normal controls, leukemia cell lines, and primary leukemia cells with low or high ITGA2 expression. In conclusions, methylation-independent ITGA2 overexpression is associated with poor prognosis in AML.

A bistable optical-electrical duple switch belongs to a class of highly satisfying intelligent materials that can transform optical and electrical responses simultaneously in one device. A perovskite-type high-temperature phase transition compound with one-dimensional chain-like crystal structure, ([(CH

Dysregulation of ID proteins is a frequent event in various human cancers and has a direct role in cancer initiation, maintenance, progression and drug resistance. Our previous study has revealed ID1 expression and its prognostic value in acute myeloid leukemia (AML). Herein, we further reported ID2 expression and its clinical significance in AML. Real-time quantitative PCR was performed to detect ID2 transcript level in bone marrow mononuclear cells of 145 de novo AML patients. ID2 expression was significantly up-regulated in AML patients compared with controls. ID2 overexpression occurred with the highest frequency in poor karyotype (10/17, 59%), lower in intermediate karyotype (35/83, 42%), and the lowest in favorable karyotype (7/40, 18%). Moreover, high ID2 expression correlated with lower complete remission (CR) rate, shorter overall survival, and acted as an independent prognostic biomarker in whole-cohort AML and non-M3-AML patients. Importantly, the prognostic value of ID2 expression in AML was validated by The Cancer Genome Atlas (TCGA) data. In the follow-up of patients, ID2 expression at CR phase was decreased than at the time of diagnosis, and was increased again at the time of relapse. These findings demonstrated that bone marrow ID2 overexpression was a frequent event in AML patients, and predicts poor chemotherapy response and prognosis.

The present study was aimed to investigate SCIN expression as well as promoter methylation and further explore their clinical relevance in acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the expression level of SCIN in 119 AML patients and 37 healthy controls. Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR were carried out to detect SCIN promoter methylation levels in 103 AML patients and 29 controls. As compared with controls, the level of SCIN transcript was significantly down-regulated in AML patients (P = 0.001), and the level of methylated SCIN promoter was significantly higher in AML patients (P = 0.001). Moreover, the level of promoter methylation was weakly negatively correlated with SCIN expression in AML patients (R = -0.265, P = 0.027). Demethylation of SCIN promoter by 5-aza-2'-deoxycytidine could restore its expression in leukemic cell line THP1. The age of SCINlow patients was significantly higher and C/EBPA mutation was significantly less than SCINhigh patients (P = 0.039 and 0.038, respectively). Moreover, the rate of complete remission (CR) of SCINlow patients was significantly lower than SCINhigh patients (P = 0.009). Kaplan-Meier analysis showed that low SCIN expression was associated with shorter overall survival (P = 0.036). Cox regression analysis demonstrated low SCIN expression was an independent poor prognostic factor (P = 0.047). Furthermore, SCIN expression was restored in those patients who achieved CR after induction therapy (P = 0.003). These findings indicate that decreased SCIN expression associated with its promoter methylation is a valuable biomarker for predicting adverse prognosis in AML patients.

An investigation into the reaction of cyanomethyltriethylammonium (CTA) halide salts with HgCl2 afforded into [(CTA)+(Hg3Cl4Br3)−]n (1) and [(CTA)+]2 (Hg2Cl6)2 − (2). The two compounds have same propeller-like quaternary ammonium cations. The anion in compound 1 was a novel two-dimensional architecture and in compound 2 was an isolated centrosymmetrical dimer. Some C H⋯N and C H⋯X (X = Cl, Br) hydrogen bonds have been found in the two compounds, which assemble the cations and anions into a three-dimensional network. Variable-temperature dielectric properties have been studied for them. There was no dielectric anomaly in 1, whereas an obvious reversible dielectric anomaly was found in 2. The differential scanning calorimetric (DSC) and variable-temperature powder XRD properties have been studied for 2. The combined results showed that compound 2 has a solid–solid phase transition from crystalline to non-crystalline.

The triethylbenzylammonium perchlorate, C13H22N+·ClO4− was synthesized and separated as block colorless crystals. DSC measurement detected that this compound undergoes a reversible phase transition at ca. 196 K with a hysteresis of 18 K width. Dielectric measurements also confirm the transition. The crystal structures determined at 93(2) K (a = 12.114(4)A, b = 14.320(5)A, c = 16.418(6)A, V = 2848.0(17)A3, Z = 8) and 291(2) K (a = 8.3891(17)A, b = 12.300(1)A, c = 14.513(1)A, V = 1497.5(3) A3, Z = 4) show that the phase transition is a type of isosymmetric change with the space group of Pbca (No. 61) in the low-temperature phase (LTP) to the space group of Pbcm (No. 57) in the room-temperature phase (RTP). The distinct difference between the LTP and the RTP structure is the different orientation for the anions and the H-bond interactions between the perchlorate anions and triethylbenzylammonium cations. Hydrogen bond interactions may play a role in the phase transition as shown by the changes in the hydrogen bonding pattern as the temperature decreased. The order–disorder type transition of the anions is probably the driving force of the phase transition.

Abnormal methylation of let-7a-3 has been found in various cancers and may consequently affect their survival. In this study, real-time quantitative methylation specific PCR (RQ-MSP) was used to determine the unmethylation level of let-7a-3 in 95 patients with myelodysplastic syndrome (MDS). The hypomethylation of let-7a-3 promoter was detected in 22 of 95 (23.2%) patients with MDS compared to 4.2% (1/24) of controls (p= 0.0419). Moreover, the frequency of let-7a-3 hypomethylation was higher in older patients (≥70 years) than in younger patients (70 years). No significant difference was observed in distribution of WHO, IPSS, and cytogenetic classification. However, hypomethylated patients had significantly shorter overall survival than those without hypomethylation (p= 0.007). Moreover both Kaplan-Meier and Multivariate Cox analyses confirmed that let-7a-3 hypomethylation was an independent prognostic risk factor in cohorts of MDS patients with lower-risk disease. Our study suggested that let-7a-3 hypomethylation may predict poor outcome in MDS.

To investigate the methylation status of miR-378 promoter in chronic myeloid leukemia (CML) and to analyze its clinical significance.The unmethylation level of miR-378 gene promoter in bone marrow mononuclear cells of 25 healthy donors and 53 patients with CML was detected by using real-time quantitative methylation-specific PCR (RQ-MSP).The hypomethylation of miR-378 gene promoter was found in 17/53 (32.1%) patients, but only in 1/25 (4.0%) of controls. The difference between the two groups was very statistically significant (P0.01). The frequency of miR-378 unmethylation in CML patients at chronic phase (CP), accelerated phase (AP) and blastic phase (BP) was 35.0% (14/40), 40.0% (2/5), and 12.5% (1/8), respectively. However, there were no significant differences in the unmethylation level of miR-378 among CML patients at different sexes, stages and karyotypes. No significant differences could be observed in age, white blood cell counts, platelet count, hemoglobin level and BCR/ABL1 transcript level (P0.05). CONCLUDSION: The miR-378 hypomethylation is a common molecular event in CML, especially at chronic or accelerated phases.

Bis(triethylbenzylammonium) tetrachlorocobaltate(II), (C13H22N+)2·CoCl42– was synthesized and separated as blue block crystals. DSC measurement detected that this compound undergoes a reversible phase transition at ca. 336 K with a hysteresis of 10 K. Dielectric measurements confirm the transition at ca. 336 K. The crystal structures determined at 291(2) K (a = 16.72 A, b = 9.32 A, c = 20.36 A, β = 106.90°, V = 3035.1 A3, Z = 4) and 353(2) K (a = 20.16 A, b = 9.35 A, c = 34.29 A, β = 108.61°, V = 6126.7 A3, Z = 8) show that the phase transition is a type of isostructural change with the same space group P21/c (No. 14). The most distinct difference between the two structures in high-temperature phase (HTP) and room-temperature phase (RTP) is the different molar ratios of configurations for the cations. The rotation of ethyl groups bonding with the N atom between the propeller-like configuration and butterfly-like configuration is probably the driving force to the phase transition. Non-classic hydrogen bonding effect on the transition was shown to be negligible.

A new 1:1 inclusion complex, 4-ethylanilinium tetrafluoroborate–1,4,7,10,13,16–hexaoxacyclooctadecane(1/1), formed between 18-crown[6] and 4-ethylanilinium tetrafluoroborate undergoes a reversible ferroelastic phase transition at ca. 180 K, as evidenced by DSC measurement with a hysteresis of 1.3 K and the variable-temperature crystal structure determinations. The single crystal X-ray diffraction data obtained at 113 and 298 K suggests that the phase transition undergoes from a room temperature paraelectric phase with a space group of P nma to a low temperature paraelectric one with a space group of P 2 1 /c, the symmetry breaking occurs with an Aizu notation of mmmF2/m . The phase transition seems to be associated with slight swing of the ethyl group of the cation brought about by reduced strength of the hydrogen bonds at elevated temperature.

Dendritic Ni33.8Co66.2 alloy microstructures with hexagonal closed-packed phase have been prepared in large-scale by a simple and facile solution phase chemical route, while flowerlike Ni33.4Co66.6 in size of 2.5–5.5 μm was synthesized by solvothermal routes. Experimental results show that the reaction temperature, total concentration of [Ni2+] + [Co2+], and kinds of solvent and surfactants are key factors for controlling the morphology and crystal phase of the NiCo alloy. The possible formation mechanism for the Ni33.8Co66.2 dendrites has been discussed. Magnetic measurements revealed that both of the NiCo2 alloys obtained are ferromagnetic at room temperature. The saturation magnetization value of the Ni33.8Co66.2 dendrites (163.55 emu/g) is lower than that of the flowerlike Ni33.4Co66.6 (195.79 emu/g), but the Ni33.8Co66.2 dendritic structures exhibit an enhanced coercivity value. NiCo2 alloys with different shapes (Ni33.8Co66.2 dendrites and flowerlike Ni33.4Co66.6) have been used as reusable heteroge...

Treatment of o-carborane, n-butyllithium, selenium, and [(p-cymene)RuCl2]2 under argon leads to the complexes (p-cymene)Ru(Se2C2B10H10) (1), [(p-cymene)RuCl(Se−SeC2B10H11)][(p-cymene)Ru(Se2C2B10H10...

The reaction of the 16e half-sandwich complex CpCo[S2C2B10H10] (1S) with phenylacetylene at ambient temperature led to 2S, 3S, and 4S. In 3S the alkyne is twofold inserted into one of the Co−S bond...

A new organic-inorganic hybrid switchable and tunable dielectric compound, [(CH3)4P]4[Mn(SCN)6] (1), exhibits three distinct dielectric states above room temperature and undergoes two reversible solid-state phase transitions, including a structural phase transition at 330 K and a ferroelastic phase transition with the Aizu notation of mmmF2/m at 352 K. The variable-temperature structural analyses disclose that the origin of the phase transitions and dielectric anomalies can be ascribed to the reorientation or motion of both the [(CH3)4P](+) cations and [Mn(SCN)6](4-) anions in solid-state crystals.

To explore efficacy enhancing and detoxification roles of Jiedu Quyu Zishen Recipe (JQZR) in treating systemic lupus erythematosus (SLE) by studying its effect on Toll like receptor 9 (TLR9) signal pathway of murine macrophage cells after JQZR stimulated CpG oligodeoxynucletide (CpG ODN).Murine macrophage cells in vitro cultured were randomly divided into 4 groups, i.e., the blank serum group, the CpG ODN stimulus group, the CpG ODN + dexamethasone group, the CpG ODN + medicated serum group. Murine macrophage cells were collected after 24-h intervention. The expression of TLR9, myeloid differentiation factor 88 (MyD88), NF-KB, IFN-α mRNA were analyzed by RT-PCR. The expression of TLR9 and NF-κB protein were analyzed by Western blot. Changes of the NF-KB transcriptional activity were assayed by Dual-Luciferase reporter assay system.mRNA expressions of TLR9, MyD88, NF-κB, and IFN-α, protein expressions of TLR9 and NF-κB, and NF-κB transcriptional activities were enhanced, showing statistical difference when compared with those of the blank serum group (P0. 05, P0. 01). Compared with the CpG ODN stimulus group, mRNA expressions of MyD88, NF-κB, and IFN-α, the protein expression of NF-κB and the NF-κB transcriptional activities decreased in the CpG ODN + dexamethasone group with statistical difference (P0. 01). Compared with the CpG ODN stimulus group, mRNA expressions of TLR9, MyD88, NF-κB, and IFN-α, protein expressions of TLR9 and NF-κB, and NF-κB transcriptional activities were decreased in CpG ODN+ medicated serum group with statistical difference (P0. 01).Efficacy enhancing and detoxification roles of JQZR in treatment of SLE might be realized through regulating TLR9 signal pathways.

Aberrant methylation of let-7a-3 promoter has been observed in various malignancies. However, the clinical relevance of let-7a-3 methylation remains poorly known in acute myeloid leukemia (AML). This study was to investigate the let-7a-3 methylation status and to explore its clinical significance in AML. let-7a-3 promoter was significantly hypomethylated in AML patients compared to controls (median 4.51 vs 0.49) (P = 0.0003). Receiver operating characteristic curve (ROC) analysis discriminated all patients or cytogenetically normal patients from controls with an areas under the ROC curve (AUC) of 0.737 or 0.783, respectively (P

The crystal structure of the title novel one-dimensionalABX3-type organic–inorganic hybrid complex {(C10H16N)[CdCl3]}n, (I), consists of benzyltrimethylammonium (Me3BzN+) cations and one-dimensional anionic {[Cd(μ-Cl)3]−}∞chains. Each CdIIcentre is hexacoordinated by bridging chloride ligands, giving a slightly distorted octahedral Cd(μ-Cl)6arrangement. The octahedra are linked by two opposite shared faces, giving rise to an almost perfectly linear anionic {[Cd(μ-Cl)3]−}∞chain in thea-axis direction. Me3BzN+cations located in the inter-chain spaces balance the charge. Noncovalent static attracting forces (Coulombic and van der Waals forces) and nonclassical C—H...Cl hydrogen-bond interactions stabilize the crystal structure.

[(p-cymene)RuCl2]2 reacts with 1,2-dicarba-closo-dodecaborane-1,2-dithiolate in the presence of excess sulfur to generate the first dinuclear complex, (p-cymene)Ru(μ-S2)Ru(S2C2B10H10)2 (1). Treatment of 1 with alkynes affords the addition complexes (p-cymene)Ru(μ-S2)Ru(S2C2B10H10)2(R1CCR2) (R1 = H (CO2Me), R2 = CO2Me (H), 2a (2b); R1 = C6H5, R2 = H, 3b; R1 = R2 = CO2Me, 4).